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阿霉素和可溶性姜黄素的可吸入生物响应性壳聚糖微球增强了肺癌细胞中的药物递送。

Inhalable bioresponsive chitosan microspheres of doxorubicin and soluble curcumin augmented drug delivery in lung cancer cells.

作者信息

Jyoti Kiran, Pandey Ravi Shankar, Kush Preeti, Kaushik Dinesh, Jain Upendra Kumar, Madan Jitender

机构信息

Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab 140307, India.

SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur, India.

出版信息

Int J Biol Macromol. 2017 May;98:50-58. doi: 10.1016/j.ijbiomac.2017.01.109. Epub 2017 Jan 25.

Abstract

In present investigation, doxorubicin (Dox) and soluble curcumin (Cur-2-HP-β-CD-complex) combination was simultaneously loaded in inhalable bioresponsive chitosan microspheres (Dox/Cur-2-HP-β-CD-complex-elastin-CMs) bearing a substrate-stimuli, elastin. The mean particle size and mean aerodynamic diameter of inhalable bioresponsive microspheres displayed noteworthy differences after incorporation of elastin. Moreover, combination of Dox and soluble curcumin was molecularly dispersed in microspheres matrix as substantiated by a range of spectral techniques. Inhalable bioresponsive microspheres released astonishingly higher amount of Dox in presence of elastase enzyme at pH∼5.5 in comparison to pH∼7.4. However, the release of soluble curcumin from tailored bioresponsive microspheres in presence of elastase enzyme was independent of pH. Consistently, inhalable bioresponsive microspheres exhibited outstandingly lower IC of 3.4-μM in comparison to 6.5-μM of inhalable drug loaded microspheres (Dox/Cur-2-HP-β-CD-complex-CMs) bearing no elastin, against A549, non-small cell lung cancer cells. The superior therapeutic profile of inhalable bioresponsive microspheres may be attributed to enhanced drug release and consequently augmented drug exposure to A549 cells expressing elastase enzyme. In this way, stimuli triggered drug release from tailored inhalable bioresponsive microspheres boosted the phenomena of apoptosis in A549 cells. In conclusion, Dox/Cur-2-HP-β-CD-complex-elastin-CMs warrant further in-vivo tumor regression study to prove its therapeutic efficacy.

摘要

在本研究中,阿霉素(Dox)和可溶性姜黄素(Cur-2-HP-β-CD复合物)同时负载于具有底物刺激物弹性蛋白的可吸入生物响应性壳聚糖微球(Dox/Cur-2-HP-β-CD复合物-弹性蛋白-CMs)中。加入弹性蛋白后,可吸入生物响应性微球的平均粒径和平均空气动力学直径显示出显著差异。此外,一系列光谱技术证实,Dox和可溶性姜黄素的组合在微球基质中呈分子分散状态。与pH值约为7.4相比,在pH值约为5.5且存在弹性蛋白酶的情况下,可吸入生物响应性微球释放出惊人数量的Dox。然而,在存在弹性蛋白酶的情况下,定制的生物响应性微球中可溶性姜黄素的释放与pH值无关。一致地,与不含弹性蛋白的可吸入载药微球(Dox/Cur-2-HP-β-CD复合物-CMs)的6.5 μM相比,可吸入生物响应性微球对非小细胞肺癌A549细胞表现出显著更低的3.4 μM半数抑制浓度(IC)。可吸入生物响应性微球卓越的治疗效果可能归因于药物释放增强,从而增加了药物与表达弹性蛋白酶的A549细胞的接触。通过这种方式,刺激触发定制的可吸入生物响应性微球释放药物,增强了A549细胞中的凋亡现象。总之,Dox/Cur-2-HP-β-CD复合物-弹性蛋白-CMs有待进一步进行体内肿瘤消退研究,以证明其治疗效果。

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